Our second research area involves the computer-aided design and chemical synthesis of novel bifunctional organic reagents to cross-link hemoglobin and double helical nucleic acids. The modified cell-free hemoglobins are to be used as substitutes for blood as oxygen carriers in emergency transfusions. There are two major problems associated with unmodified cell-free hemoglobins to be employed as blood substitutes: a) they are easily and quickly eliminated by kidneys, and b) their oxygen affinity is too high to adequately transport oxygen from lungs to tissues. The cross-linked hemoglobins are anticipated to eliminate both of these problems. The need for a blood substitute is becoming increasingly pressing in view of the scarcity of blood especially when rare types are needed, the possible transmission of diseases associated with blood transfusion such as AIDS and hepatitis, the limitations on storage stability of intact blood, the necessity for blood typing before transfusion, and not to mention other religious reasons, for example, the reluctance of Jehovah's witnesses to accept an alien blood. Cross-linking nucleic acid bases within a double-helix has implications in cancer chemotherapy, and in probing nucleic acid structure and function. Cross-linking reagents that have been extensively used for investigating structure and function of nucleic acids include synthetic reagents such as nitrogen mustards and natural products like psoralens, anthramycins, CC-1065, and mitomycins. Many of these cross-linking reagents have anticancer properties as they interfere with cellular replication of nucleic acids. The synthetic cross-linking reagents were characterized by both low- and high-resolution mass spectrometry, employing EI, CI and FAB ionization.